ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma
Abstract Background Lung adenocarcinoma (LUAD) is a common subtype of non‐small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA‐specific 1 (ADAR1) is an RNA editing enzyme that catal...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-07-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6044 |
| _version_ | 1827897489495162880 |
|---|---|
| author | Wendi Yang Kehong Chen Qian Yu Rongxin Liao Hengqiu He Yuan Peng Zhenzhou Yang Xiaoyue Zhang |
| author_facet | Wendi Yang Kehong Chen Qian Yu Rongxin Liao Hengqiu He Yuan Peng Zhenzhou Yang Xiaoyue Zhang |
| author_sort | Wendi Yang |
| collection | DOAJ |
| description | Abstract Background Lung adenocarcinoma (LUAD) is a common subtype of non‐small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA‐specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine‐to‐inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1. Methods The expression of ADAR1 was analyzed in The Cancer Genome Atlas ‐LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan‐Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell‐type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD. Results ADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p < 0.01), advanced tumor stage (p < 0.05), and poor patient prognosis (p < 0.01), thus indicating that increased ADAR1 contributed to the progression of LUAD. LUAD with high ADAR1 expression can metastasize to lymph nodes that express more ADAR1 than the primary lesion. In addition, M0 macrophages and M2 macrophages increased and CD4+T cells decreased in LUAD tissues with high ADAR1 expression. And the expression of ADAR1 in lymph node metastases was negatively correlated with the contents of CD4+T cells (p = 0.0017) and M1 macrophages (p = 0.0037). Conclusion The findings of our study suggested that ADAR1 may be useful in predicting prognosis and LNM in LUAD, and may serve as a promising immune‐related molecular target for LUAD patients. |
| first_indexed | 2024-03-12T22:49:51Z |
| format | Article |
| id | doaj.art-2b1cf4340d704a309a822136aac3c529 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-12T22:49:51Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-2b1cf4340d704a309a822136aac3c5292023-07-20T12:57:16ZengWileyCancer Medicine2045-76342023-07-011213148201483210.1002/cam4.6044ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinomaWendi Yang0Kehong Chen1Qian Yu2Rongxin Liao3Hengqiu He4Yuan Peng5Zhenzhou Yang6Xiaoyue Zhang7Department of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Cancer Center The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaAbstract Background Lung adenocarcinoma (LUAD) is a common subtype of non‐small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA‐specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine‐to‐inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1. Methods The expression of ADAR1 was analyzed in The Cancer Genome Atlas ‐LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan‐Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell‐type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD. Results ADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p < 0.01), advanced tumor stage (p < 0.05), and poor patient prognosis (p < 0.01), thus indicating that increased ADAR1 contributed to the progression of LUAD. LUAD with high ADAR1 expression can metastasize to lymph nodes that express more ADAR1 than the primary lesion. In addition, M0 macrophages and M2 macrophages increased and CD4+T cells decreased in LUAD tissues with high ADAR1 expression. And the expression of ADAR1 in lymph node metastases was negatively correlated with the contents of CD4+T cells (p = 0.0017) and M1 macrophages (p = 0.0037). Conclusion The findings of our study suggested that ADAR1 may be useful in predicting prognosis and LNM in LUAD, and may serve as a promising immune‐related molecular target for LUAD patients.https://doi.org/10.1002/cam4.6044adenosine deaminase 1lung adenocarcinomalymph node metastasistumor microenvironment |
| spellingShingle | Wendi Yang Kehong Chen Qian Yu Rongxin Liao Hengqiu He Yuan Peng Zhenzhou Yang Xiaoyue Zhang ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma Cancer Medicine adenosine deaminase 1 lung adenocarcinoma lymph node metastasis tumor microenvironment |
| title | ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| title_full | ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| title_fullStr | ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| title_full_unstemmed | ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| title_short | ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| title_sort | adar1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma |
| topic | adenosine deaminase 1 lung adenocarcinoma lymph node metastasis tumor microenvironment |
| url | https://doi.org/10.1002/cam4.6044 |
| work_keys_str_mv | AT wendiyang adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT kehongchen adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT qianyu adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT rongxinliao adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT hengqiuhe adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT yuanpeng adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT zhenzhouyang adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma AT xiaoyuezhang adar1isaprognosticbiomarkerandiscorrelatedwithimmuneinfiltrationinlungadenocarcinoma |